The overall aim of the Program Project Grant (PPG) is to understand the genetic basis for fear, anxiety and anxiety disorders in humans by identifying variant forms of genes that may contribute to pathological anxiety states. The underlying idea is that both learned and innate fear are tractable targets for genetic analyses in mice and humans. To accomplish this portion of the PPG dealing with human anxiety disorders Project 4 will provide well-characterized clinical samples and DNA from subjects with selected anxiety disorders (panic disorder, social anxiety disorder, and controls). Dimensional assessments of anxiety related temperaments, which cut across all clinical groups will provide another method for sample stratification. The clinical disorders have been selected where there is indication of heritability from family and/or twin studies; the clinical phenotypes are well defined and there is suggestive evidence for a relationship with fear conditioning and/or its neurobiological substrate and where hypotheses about candidate genes based on marker, treatment or pathophysiologic studies can be developed. To maximize the likelihood that we are selecting cases with genetic etiology, we will select cases from families with multiple affected individuals. The dimensional assessments have been selected because of prior promising associations with specific polymorphisms related to anxiety and evidence for heritability. Since issues of design and control groups have not been resolved, we will use both family based "triads" (probands and two biological parents) and population controls (matched for ethnicity). The central hypothesis is that there are similarities in fear conditioning circuitry between animal models and human and that genes involved in the pathways associated with fear conditioning or innate fear may be involved in the development of human anxiety disorders, particularly panic disorder, social anxiety disorder (social phobias), and/or neuroticism or anxiety sensitivity. The specific aims of this project are: identification, clinical characterization and DNA extraction of subjects with panic disorder (N= 150); social anxiety disorder (social phobia) (N=150); selected to be at high genetic risk for anxiety disorders; non ill matched controls also assessed on quantitative trait dimension (N=150). We will also collect bloods from the biological parents of the panic and social anxiety disorder probands.